Esophagogastric Junction Cancer Patients Research Articles

Prognostic nutritional index is a prognostic factor for patients with gastric cancer and esophagogastric junction cancer undergoing proximal gastrectomy with esophagogastrostomy by the double-flap technique: A secondary analysis of the rD-FLAP study

PurposeAlthough proximal gastrectomy (PG) is commonly used in patients with upper gastric cancer (GC) and esophagogastric junction (EGJ) cancer, long-term prognostic factors in these patients are poorly understood. The double-flap technique (DFT) is an esophagogastrostomy with anti-reflux mechanism after PG; we previously conducted a multicenter retrospective study (rD-FLAP) to evaluate the short-term outcomes of DFT reconstruction. Here, we evaluated the long-term prognostic factors in patients with upper GC and EGJ cancer. MethodsThe study was conducted as a secondary analysis of the rD-FLAP Study, which enrolled patients who underwent PG with DFT reconstruction, irrespective of disease type, between January 1996 and December 2015. ResultsA total of 509 GC and EGJ cancer patients were enrolled. Univariate and multivariate analyses of overall survival demonstrated that a preoperative prognostic nutritional index (PNI) < 45 (p < 0.001, hazard ratio [HR]: 3.59, 95% confidential interval [CI]: 1.93–6.67) was an independent poor prognostic factor alongside pathological T factor ([pT] ≥2) (p = 0.010, HR: 2.29, 95% CI: 1.22–4.30) and pathological N factor ([pN] ≥1) (p = 0.001, HR: 3.27, 95% CI: 1.66–6.46). In patients with preoperative PNI ≥45, PNI change (<90%) at 1-year follow-up (p = 0.019, HR: 2.54, 95%CI: 1.16–5.54) was an independent poor prognostic factor, for which operation time (≥300 min) and blood loss (≥200 mL) were independent risk factors. No independent prognostic factors were identified in patients with preoperative PNI <45. ConclusionsPNI is a prognostic factor in upper GC and EGJ cancer patients. Preoperative nutritional enhancement and postoperative nutritional maintenance are important for prognostic improvement in these patients.

Impacts of neoadjuvant therapy on the number of dissected lymph nodes in esophagogastric junction cancer patients

BackgroundNeoadjuvant therapy favors the prognosis of various cancers, including esophagogastric junction cancer (EGC). However, the impacts of neoadjuvant therapy on the number of dissected lymph nodes (LNs) have not yet been evaluated in EGC.MethodsWe selected EGC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2006–2017). The optimal number of resected LNs was determined using X-tile software. Overall survival (OS) curves were plotted with the Kaplan–Meier method. Prognostic factors were evaluated using univariate and multivariate COX regression analyses.ResultsNeoadjuvant radiotherapy significantly decreased the mean number of LN examination compared to the mean number of patients without neoadjuvant therapy (12.2 vs. 17.5, P = 0.003). The mean LN number of patients with neoadjuvant chemoradiotherapy was 16.3, which was also statistically lower than 17.5 (P = 0.001). In contrast, neoadjuvant chemotherapy caused a significant increase in the number of dissected LNs (21.0, P < 0.001). For patients with neoadjuvant chemotherapy, the optimal cutoff value was 19. Patients with > 19 LNs had a better prognosis than those with 1–19 LNs (P < 0.05). For patients with neoadjuvant chemoradiotherapy, the optimal cutoff value was 9. Patients with > 9 LNs had a better prognosis than those with 1–9 LNs (P < 0.05).ConclusionsNeoadjuvant radiotherapy and chemoradiotherapy decreased the number of dissected LNs, while neoadjuvant chemotherapy increased it in EGC patients. Hence, at least 10 LNs should be dissected for neoadjuvant chemoradiotherapy and 20 for neoadjuvant chemotherapy, which could be applied in clinical practice.

Clinical utility of lymphocyte to C-reactive protein ratio in predicting survival and postoperative complication for esophago-gastric junction cancer

BackgroundThere are still no useful predictive biomarkers for esophago-gastric junction (EGJ) cancer. We compared 15 candidate inflammation-based markers and investigated the clinical impact of the selected biomarker. MethodsOne hundred three patients with EGJ cancer between 2002 and 2020 were enrolled, and associations between clinicopathological data and inflammatory biomarkers were retrospectively analyzed. Area under the curve (AUC) values of 15 candidate biomarkers were compared in receiver operating characteristic (ROC) curves regarding overall survival (OS). Clinical impacts of the selected marker were further investigated regarding long-term prognosis, postoperative complications, and preoperative chemotherapy effects. ResultsLymphocyte/CRP ratio (LCR) demonstrated the highest AUC (0.68552) and was chosen as a candidate biomarker. The high LCR group (LCR >4610) demonstrated significantly better OS (p < 0.0001) and relapse-free survival (RFS) (p < 0.0001) compared with the low LCR group (LCR ≤4610), and preoperative LCR was an independent prognostic factor for both OS (HR 4.97, 95% CI:2.24–11.58; p < 0.0001) and RFS (HR 2.84, 95% CI:1.33–6.14, p = 0.007) in EGJ cancer patients. Another cut-off value was established for postoperative complications, and the incidence rates were significantly higher in the low LCR group (LCR ≤12000) than in the high LCR group (LCR >12000) for all postoperative complications, infectious complications, and surgical site infection (p = 0.013, p = 0.016, and p = 0.030, respectively). Furthermore, patients with decreased LCR after preoperative chemotherapy demonstrated significantly worse RFS compared with patients with increased LCR (p = 0.043). ConclusionsLCR is a potential biomarker to predict long-term prognosis as well as occurrence of postoperative complications in patients with EGJ cancer.

Modified Glasgow prognostic score (mGPS) is correlated with sarcopenia and dominates the prognostic role of baseline body composition parameters in advanced gastric and esophagogastric junction cancer patients undergoing first-line treatment from the phase III EXPAND trial

Sarcopenia represents an established adverse prognostic factor in cancer patients. Consequently, different means to counteract sarcopenia have been proposed to improve cancer treatment. Computed tomography (CT)-based measurements, also labor intensive, are well validated for the analysis of sarcopenia. As inflammation plays a key role in the development of sarcopenia, we here studied the role of the modified Glasgow prognostic score (mGPS), consisting of inflammation parameters plasma C-reactive protein (CRP) and albumin, to predicting sarcopenia and adipose tissue-related body composition (BC) parameters at baseline and their changes during treatment and to analyze its prognostic role in conjunction with BC parameters. CT measurements of BC parameters were carried out at baseline and week 12 in patients with advanced gastric or esophagogastric junction cancer from the phase III EXPAND trial, undergoing first-line platinum-fluoropyrimidine chemotherapy. mGPS was calculated from baseline CRP and albumin plasma levels. Pearson correlation and Cox regression analyses were carried out. mGPS is strongly prognostic for overall survival (OS). Baseline mGPS is significantly correlated with baseline mean muscle attenuation (MA; P < 0.0001). Baseline mGPS did not predict a decline in muscle or adipose tissue parameters during 12 weeks of treatment and a decline in muscle or adipose tissue parameters was not prognostic for OS. MA lost its prognostic role for OS when mGPS or CRP was entered into the Cox models. Eastern Cooperative Oncology Group performance status together with CRP or mGPS remained the sole baseline prognostic factors for OS. Our findings support a model where tumor-mediated inflammatory response represents a strong prognostic factor, which is causally related to sarcopenia, but with no direct causal path from sarcopenia to survival. Therefore, therapeutic targeting of systemic inflammation should be further explored as a promising strategy to improve both sarcopenia and the efficacy and tolerability of cancer treatment.

Esophagectomy combined with off-pump coronary artery bypass grafting through left posterolateral incision is safe and feasible for esophageal cancer associated with coronary artery disease.

Controversy still exists as to whether surgical treatment has any impact on the long-term survival of esophageal cancer (EC) patients with coronary artery disease treated with curative esophagectomy combined with off-pump coronary artery bypass grafting (OPCABG). Therefore, the aim of this study was to introduce and assess the effect of esophagectomy combined with OPCABG on both short- and long-term outcomes. From January 2010 to January 2015, 1428 EC or esophagogastric junction cancer patients underwent surgical treatment at Henan Chest Hospital, Zhengzhou, China. The clinical data of 25 patients who underwent EC resection through a left thoracotomy following OPCABG and the perioperative characteristics and follow-up results were analyzed. The majority of the patients were male, and the EC stage was predominantly cT2N0-1M0 II. The most common pathological types were squamous cell carcinoma. The EC surgeries consisted of 15 chest anastomosis procedures and 10 cervical anastomosis procedures with aortocoronary graft implantation (mean: 2.36 grafts per patient). The mean total operative time was 330.8 ± 83.5minutes. The median intensive care unit and hospital lengths of stay were 1.72 and 21.16days, respectively. Resection without macroscopic residual disease (R0) was achieved in all of the patients. The most frequent complications included pulmonary infections (24%), arrhythmias (24%), pleural effusion (12%), and esophageal anastomotic leakage (8%). There were no postoperative deaths or myocardial infarctions within 30 days after the surgery. The overall 1-, 3-, and 5-year survival rates were 88%, 40%, and 24%, respectively, with a median survival time of 43months. In the short-term, radical resection of EC following OPCABG is a safe and feasible treatment with low postoperative mortality rates. In the long-term, simultaneous surgery is acceptable and is associated with favorable overall and disease-free survival.

HER2 gene assessment in liquid biopsy of gastric and esophagogastric junction cancer patients qualified for surgery

BackgroundAmplification of HER2 gene (ERBB2) and overexpression of HER2 protein on cancer cells are found in 10–26% of gastric cancer (GC) and esophagogastric junction cancer (EGJC). Gene copy number variation (CNV) could be detected in these patients in liquid biopsy and in cancer cells.MethodsWe analysed HER2 gene CNV used qPCR method in 87 sera collected from GC and EGJC patients before surgical treatment and in 40 sera obtained from healthy donors. HER2 gene CNV was also assessed in formalin-fixed paraffin-embedded (FFPE) tumor tissue. Furthermore, we assessed the number of HER2 gene copies and HER2 expression in cancer cells using the fluorescent in situ hybridization method (FISH) and immunohistochemistry (IHC).ResultsWe found that the HER2 gene copy number in liquid biopsy was higher in GC and EGJC patients compared to healthy people (p = 0.01). Moreover, EGJC patients had higher number of HER2 gene copies than healthy donors (p = 0.0016). HER2 CNV examination could distinguish healthy individuals and patients with gastric or esophagogastric junction cancers with sensitivity and specificity of 58% and 98% (AUC = 0.707, 95% CI 0.593–0.821, p = 0.004). We found that patients with a high copy number of the HER2 gene in the tumor tissue assessed by qPCR (but not by FISH) have significantly more often a high number of HER2 gene copies in liquid biopsy (p = 0.04).ConclusionsWe suggested that HER2 testing in liquid biopsy could be used as an auxiliary method to analysis of HER2 status in tumor tissue in gastric or esophagogastric junction cancers.

Multimodal treatments for resectable esophagogastric junction cancer: a systematic review and network meta-analysis.

Background:Currently, preoperative chemoradiotherapy, perioperative chemotherapy and preoperative chemotherapy are recommended by NCCN, ESMO and Japanese guidelines respectively for resectable esophageal and junctional cancer. However, these recommendations are mainly based on esophageal cancer research. Therefore, specific for esophagogastric junction cancer, we conducted the first systematic review and network meta-analysis to rank all potential treatments simultaneously and hierarchically.Methods:Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO and ESMO Meeting Library from inception to September 2018. Regarding time-to-event survival data, randomized controlled trials featuring comparisons between different multimodal treatments against resectable esophagogastric junction cancer were eligible. Overall survival was the endpoint. Network calculation was based on a random-effects model and the relative ranking of each node was numerically indicated by P-score (CRD42018110369, registration identifier of the meta-analysis in PROSPERO.).Results:Eight studies were included in our systematic review, corresponding to 1218 patients. Regarding overall survival, ‘PreCRT’ (preoperative chemoradiotherapy) topped the hierarchy (HR 1.00, P-score = 0.823), better than ‘PeriCT’ (perioperative chemotherapy; HR 1.32, P-score = 0.591) and ‘PreCT’ (preoperative chemotherapy; HR 1.54, P-score = 0.428). In sensitivity analyses, irrespective of interchanging to fixed-effects model or removing potentially heterogeneous studies, relative rankings remained stable and ‘PreCRT’ was still the optimal node.Conclusion:Preoperative chemoradiotherapy could potentially be the optimal multimodal treatment, which displayed more overall survival benefits than perioperative chemotherapy and preoperative chemotherapy among resectable esophagogastric junction cancer patients. To further verify our pooled results, more randomized trials will be needed to compare preoperative chemoradiotherapy with perioperative chemotherapy (especially FLOT-based regimens).

Effect of preoperative monocyte-lymphocyte ratio on prognosis of patients with resectable esophagogastric junction cancer

Objective: To investigate the associations between various blood test parameters including MLR (monocyte-lymphocyte ratio) and prognosis in post-operative esophagogastric junction cancer patients. Methods: We retrospectively studied the preoperative and postoperative data of 309 patients who underwent radical surgery for esophagogastric junction cancer. The relationship between MLR, neutrophil lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and overall survival (OS) was analyzed. Results: The cutoff values of MLR、NLR and PLR were 0.201, 1.697 and 96.960, respectively. The median OS was 51.4 months for all the patients in the study group (n=309). MLR in patients with esophagogastric junction carcinoma was associated with gender, depth of invasion, histological grade, TNM stage, NLR and PLR (P<0.05). PLR was associated with tumor size, TNM stage, NLR and MLR (P<0.05). NLR was associated with gender, tumor size, TNM stage, PLR and MLR (both P<0.05). Univariate analysis showed that tumor size, depth of tumor invasion, metastasis of lymph nodes, pathological grading, nerve infiltration, lymphovascular invasion, TNM staging, PLR and MLR were associated with the median overall survival time (P<0.05). Multivariate analysis showed that TNM stage, nerve infiltration and MLR were independent prognostic predictors for patients with esophagogastric junction cancer (P<0.05), but not PLR or NLR. Setting the optimal cut-off value of the MLR in 0.201, the area under the curve was 0.603, significantly larger than that of PLR and NLR (P<0.05). Conclusions: Preoperative MLR is a very useful predictor of patients with esophagogastric junction cancer who underwent radical rescetion. Preoperative MLR> 0.201 is an independent risk factor for postoperative survival in patients with esophagogastric cancer, and PLR> 96.960 may predict a poor prognosis risk.

Experiences in the management of anastomotic leakages and analysis of the factors affecting leakage healing in patients with esophagogastric junction cancer.

It was reported in the literatures that the incidence of anastomotic leakage in patients with esophagogastric junction cancer decreased due to application of staplers and closure devices as well as gastric conduit technique in recent years, however, it increased slightly at our center since widely using the above devices and gastric conduit techniques from 2009. The objective of this study was to summarize our experiences in the management of anastomotic leakages and analyze the factors affecting leakage healing in the patients with esophagogastric junction cancer after surgical resection in recent 6 years. All patients who received surgical resections for esophagogastric junction cancer and diagnosed anastomotic leak at our center between January 2009 and December 2014 were retrospectively analyzed, we also enrolled the patients who had a longer hospital stay (>30 days) as they may develop anastomotic leak. The binary logistic regression in SPSS 16.0 was applied to analyze the factors that may affect leakage healing. Of the 1,815 surgically treated esophagogastric junction cancer patients, 91 cases were diagnosed anastomotic leakage postoperatively. The patients were divided into two groups based on the median leakage healing time (40 days) in this series: fast healing group (37 cases) and slowly healing group (54 cases). All factors that may affect the leakage healing were put into analysis by using binary logistic regression. The results of the analysis showed that leakage size (OR =1.073, P=0.004), thoracic drainage (OR =12.937, P=0.037) and smoking index ≤400 (OR =1.001, P=0.04) significantly affected the healing time, while drinking history (P=0.177), duration of fever after anastomotic leak developed (P=0.084), and hypoproteinemia after leak (P=0.169) also apparently but not significantly affect the healing time. Though many factors may affect leakage healing in the esophagogastric junction carcinoma patients, leakage size, thoracic drainage and smoking index (≤400) are the most important factors affecting the leakage healing. Placement of a chest tube beside the anastomosis area during operation for early identification and control of an anastomotic leak to minimize contamination of the mediastinum is the most important way to promote leakage healing. A chest tube placing into the purulent cavities after the patients experienced leaks is also important for the cure of leakage. More attention should be paid perioperatively to the patients who had a smoking index (≥400) and the patients who suffered fever or hypoproteinemia.

Changing patterns in presentation and therapy of esophagogastric junction cancers in the United States.

22 Background: Esophagogastric junction cancer (EGJC) has recently been included within the esophageal cancer (EC) AJCC TNM staging criteria. Trends in clinical presentation, therapeutic approach and outcomes are of interest. Methods: We identified EGJCs from the U.S. population SEER database and examined incidence, demographic, therapeutic and outcomes information. Siewert classification-related EGJC subtype-associated findings were also examined. Results: EGJC age-adjusted incidence rates (x10-5) have increased from 3.3 in 1973 to 7.5 in 2009. While the incidence rate for females has remained around 2, rates in males have increased from 6 to 13. Among 30,710 EGJC patients diagnosed between 1992 and 2009, potentially curative resection increased from 31% to 36% and radiation increased from 32% to 41% (p&lt;0.0001). For resected EGJCs, significant trends over time include: increased total LN count (mean: 15.5 vs. 12.3), fewer positive LNs (3.1 vs. 4), smaller tumor size (29% vs. 36% &gt;5 cm), lower T category (39% vs. 29% T1/2), lower N category (42% vs. 35% N0), lower stage group (29% vs. 38% stage 3/4), increased preoperative radiation (26% vs. 3%), decreased 90-day mortality (6.5 vs. 14.1%), longer overall survival (OS, median: 2.9 vs. 1.7 years) and longer disease-specific survival (median: 3.9 vs. 2.0 years) (all at p&lt;0.0001). Multivariate predictors of OS include TNM categories, age, ethnicity, radiation, and total LN count (all at p&lt;0.0001). There were significant differences in stage-for-stage OS between EC subtypes based on histology and primary tumor location, and in DSS between EGJC subtypes (Siewert I, II or III) as well. Conclusions: EGJC incidence rates, diagnosis and treatment have undergone significant changes within the U.S. population. The regional dissection extent remains an area of importance as it is associated with OS. Comparisons of various survival outcomes do not support using the same staging criteria for EGJC as for EC.

Ratio of Metastatic to Examined Lymph Nodes, a Helpful Staging System and Independent Prognostic Factor of Esophagogastric Junction Cancer

BackgroundThe incidence of the esophagogastric junction cancer is growing rapidly. The purpose of this study is to clarify the outcome of the ratio between metastatic and examined lymph nodes in esophagogastric junction cancer patients with or without 7 examined lymph nodes.MethodsA total of 3,481 patients who underwent operation are identified from the Surveillance, Epidemiology, and End Results database. Different lymph nodes resected groups are analyzed to test the lymph nodes ratio factor.ResultsThere are 2522 patients with 7 or more lymph nodes resected and 959 patients with less than 7 lymph nodes resected. Lymph nodes ratio and lymph node involvement are independent prognostic factors. But the lymph nodes ratio categories have a better prognostic value than the lymph node involvement categories. Compared with lymph node involvement categories, lymph nodes ratio categories represent patients with more homogeneous overall survival rate.ConclusionsThis study defines that the lymph nodes ratio is an independent prognostic factor for esophagogastric junction cancer. The lymph nodes ratio can prevent stage migration and may be a helpful system to predict the prognosis of esophagogastric junction cancer patients.

Gastric Stump Cancer: More Than Just Another Proximal Gastric Cancer and Demanding a More Suitable TNM Staging System

Background. Considerable controversy persists about the biological behavior of gastric stump cancer (GSC). The aim of this study is to clarify if this cancer is just another proximal gastric cancer or if it emerges as a distinctive clinicopathologic entity. Methods. This review of a prospectively collected gastric cancer database identified 73 patients with GSC in a single institution between January 1980 and June 2012 and compared them with 328 patients with proximal gastric cancer (PGC) and 291 patients with esophagogastric junction cancer (EGJC). Results. Patients with GSC were predominantly males. Eighty-three percent of GSC penetrated the subserosal or the serosal layers. The median number of lymph nodes retrieved in GSC patients was significantly lower than in PGC patients or in EGJC patients. Cumulative survival curves were not different between GSC, PGC, or EGJC patients. Unlike that observed in PGC and in EGJC, no significant differences in cumulative survival according to the TNM staging system were observed in GSC cases. Conclusions. The outcome of patients with GSC displayed significant differences when compared to those with other proximal gastric cancers concerning the lack of survival association with the TNM staging system. Therefore a more suitable staging system should be designed for these unique cancers.